Randomized Trial of Minimal Ventilator Support and Early Corticosteroid Therapy to Increase Survival Without Chronic Lung Disease in Extremely-Low-Birth-Weight Infants
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Bronchopulmonary Dysplasia
- Sponsor
- NICHD Neonatal Research Network
- Enrollment
- 220
- Locations
- 13
- Primary Endpoint
- Death or moderate to severe bronchopulmonary dysplasia
- Status
- Terminated
- Last Updated
- 10 years ago
Overview
Brief Summary
This multicenter clinical trial tested whether minimal ventilation decreases death or BPD. Infants with birth weight 501g to 1000g and mechanically ventilated before 12 hours were randomly assigned to minimal ventilation (partial pressure of carbon dioxide [PCO(2)] target >52 mm Hg) or routine ventilation (PCO(2) target <48 mm Hg) and a tapered dexamethasone course or saline placebo for 10 days, using a 2 x 2 factorial design. The primary outcome was death or BPD at 36 weeks' postmenstrual age. Blood gases, ventilator settings, and FiO2 were recorded for 10 days; complications and outcomes were monitored to discharge. The infants' neurodevelopment was evaluated at 18-22 months corrected age.
Detailed Description
Chronic lung disease (CLD), also known as bronchopulmonary dysplasia (BPD), in very premature infants has been associated with mechanical ventilation and relative adrenal insufficiency. This multicenter clinical trial tested whether minimal ventilation decreases death or BPD. Infants with birth weight 501g to 1000g and mechanically ventilated before 12 hours were randomly assigned to minimal ventilation (partial pressure of carbon dioxide \[PCO(2)\] target \>52 mm Hg) or routine ventilation (PCO(2) target \<48 mm Hg) and a tapered dexamethasone course or saline placebo for 10 days, using a 2 x 2 factorial design. The primary outcome was death or BPD at 36 weeks' postmenstrual age. Blood gases, ventilator settings, and FiO2 were recorded for 10 days; complications and outcomes were monitored to discharge. The trial was terminated by the Steering Committee when the interim analysis for the Data Safety and Monitoring Committee showed a higher rate of spontaneous gastrointestinal perforations in the dexamethasone-treated infants. Neurodevelopment was assessed at 18-22 months postmenstrual age.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Greater than 12 hrs of age and less than 10 days chronologic age
- •501-1000 gm
- •Intubated and mechanically ventilated before 12 hrs
- •Indwelling vascular catheter
- •Infants 751-100 gm must be receiving FiO2 greater than 0.30 and have received at least 1 dose of surfactant at randomization
- •Parental consent
Exclusion Criteria
- •Major congenital anomaly
- •Symptomatic non-bacterial infection
- •Permanent neuromuscular conditions that affect respiration
- •Terminal illness (defined as pH values less than 6.8 for more than 2 hours or persistent bradycardia associated with hypoxia for more than 2 hours)
- •Use of postnatal corticosteroids
Arms & Interventions
Routine ventilation without Dexamethasone
Intervention: Placebo
Minimal ventilation with Dexamethasone
Minimal ventilator support strategy (permissive hypercapnia) and early stress dose dexamethasone therapy
Intervention: Minimal mechanical ventilation management
Minimal ventilation with Dexamethasone
Minimal ventilator support strategy (permissive hypercapnia) and early stress dose dexamethasone therapy
Intervention: Dexamethasone
Minimal Ventilation without Dexamethasone
Minimal ventilator support strategy (permissive hypercapnia) and no dexamethasone therapy
Intervention: Minimal mechanical ventilation management
Minimal Ventilation without Dexamethasone
Minimal ventilator support strategy (permissive hypercapnia) and no dexamethasone therapy
Intervention: Placebo
Routine ventilation with Dexamethasone
Intervention: Routine mechanical ventilation management
Routine ventilation with Dexamethasone
Intervention: Dexamethasone
Routine ventilation without Dexamethasone
Intervention: Routine mechanical ventilation management
Outcomes
Primary Outcomes
Death or moderate to severe bronchopulmonary dysplasia
Time Frame: 36 weeks postmenstrual age
Secondary Outcomes
- Deafness(18-22 months corrected age)
- Death(18-22 months corrected age)
- Mechanical ventilation(36 weeks postmenstrual age)
- Pulmonary interstitial emphysema(36 weeks postmenstrual age)
- Pneumothorax(36 weeks postmenstrual age)
- Open-label steroids(36 weeks postmenstrual age)
- Reintubation(36 weeks postmenstrual age)
- Intracranial hemorrhage (IVH) III or IV(36 weeks postmenstrual age)
- Periventricular leukomalacia(36 weeks postmenstrual age)
- Necrotizing enterocolitis(36 weeks postmenstrual age)
- Duration of oxygen supplementation(36 weeks postmenstrual age)
- Duration of ventilation(36 weeks postmenstrual age)
- Length of hospitalization(Hospital discharge)
- Death or neurodevelopmental impairment(18-22 months corrected age)
- Neurodevelopmental impairment(18-22 months corrected age)
- Cerebral palsy(18-22 months corrected age)
- Bilateral blindness(18-22 months corrected age)
- Bayley Scales of Infant Development-Revised II Psychomotor Developmental Index (PDI)(18-22 months corrected age)
- Rehospitalizations(18-22 months corrected age)